a. Tetrazoleacetic acid Chemistry
In the Journal of Organic Chemistry, Vol. 21, (1956), pages 311-315, in an article entitled "Studies in Tetrazole Chemistry, IV, Tetrazoleacetic Acids and Esters", C. R. Jacobson et al. describe a method for preparing 5-substituted-1-tetrazole-1-acetic esters by reacting an ester of an N-acylated .alpha.-amino acid sequentially with phosphorus pentachloride and hydrazoic acid.
In the Journal of Organic Chemistry, Vol 22, (1957), pages 933-936, in an article entitled "Synthesis of 1-Substituted Tetrazoles" F. G. Fallon et al. describe the preparation of seven 1-alkyltetrazoles by interaction of alkyl isocyanides and hydrazoic acid in benzene solution.
In the Journal of Organic Chemistry, Vol. 27, pp. 2085-2087 (1962) in an article entitled "The Formation of Tetrazoles by the Condensation of Organic Azides with Nitriles", W. R. Carpenter describes the preparation of various 1,5-disubstituted tetrazoles by the thermal condensation of alkyl or aryl azides with electronegative haloalkyl nitriles, e.g., trifluoromethylnitrile, perfluoropropylnitrile, none of which products was a tetrazoleacetate ester or acid.
Angew. Chem. internat. Edit., Vol. 2 (1963) No. 10, on page 579 suggests that only electron-poor C N triple bonds of ethyl cyanoformate or of perfluoroalkyl cyanides are capable of adding organic azides to form 5-trifluoromethyl-1-alkyl-1H-tetrazoles; however, the publication does not define the conditions of reaction.
U.S. Pat. No. 3,073,731 granted Jan. 15, 1963 discloses, inter alia, the preparation of ethyl 1- and 2-tetrazoleacetates from tetrazole and ethyl bromoacetate. The products are said to be useful as plasticizers.
In The Canadian Journal of Chemistry, Vol. 47, (1969) pages 813-819, R. Raap et al. disclose the synthesis of several 1-, 2-, and 5-tetrazoleacetate esters by the alkylation of the triethylammonium salts of tetrazole with ethyl bromoacetate or methyl chloroacetate. This reference also discloses the hydrolysis of the esters to the acids and contains a bibliography to other related work. This reference also discloses the preparation of methyl 5 -trifluoromethyl-1-tetrazolylacetate from trifluoroacetonitrile and methyl azidoacetate under the conditions given by Carpenter. [W. R. Carpenter, J. Org. Chem. 27 2085 (1962) ]
B. Cephalosporin Antibiotic Patents
In U.S. Pat. No. 3,468,874 there is disclosed the preparation of some tetrazolylacetate esters by reacting, e.g., tert-butyl isocyanoacetate with hydrazoic acid or by treating a mixture of tetrazole and triethylamine in acetone with ethyl bromoacetate. The patent claims some penicillin and some cephalosporin compounds having the tetrazoleacetamido group in the 6-position of the penicillin or in the 7-position of the cephalosporin.
Netherlands Pat. No. 67/17107, published June 17, 1968 discloses the formation of 3-(substituted-tetrazolemethyl)cephalosporins by reacting a 3-azidomethylcephalosporin ester with certain dipolarophiles such as an alkoxycarbonyl cyanide.
There still exists a need to provide alternate and improved processes for preparing 1-tetrazoleacetate esters and acids and intermediates therefor which can be used for a variety of purposes, some of which are suggested by the above prior art summary. None of the prior art, to applicant's knowledge, suggests the improved, simplified process described herein or the intermediates produced therefrom.
It is an object of this invention to provide a simplified process for preparing various substituted and unsubstituted 1-tetrazoleacetate esters and acids.
It is a further object of this invention to provide novel 5-substituted-1-tetrazoleacetate esters which are readily convertible to 1H-tetrazole-1-acetic acid.
It is a specific object of this invention to provide a process for preparing 1H-tetrazole-1-acetic acid which is of interest for use in preparing penicillin and cephalosporin antibiotics such as those described in the above mentioned U.S. Pat. No. 3,468,874 as well as those described in U.S. Pat. No. 3,516,997.